The research described in this proposal details a procedure for detecting neurotransmitters and their metabolites at subnanomolar levels. The method centers around surface enhanced Raman scattering (SERS) spectroscopy with colloidal noble metals. It has been shown that colloidal silver and gold can be used to detect dopamine and norepinephrine at low nanomolar levels. These levels are achieved with normal Raman and SERS. We propose a method of tagging the neurotransmitters with a novel "reporter" molecule that converts them into resonantly enhanced molecules. This will increase the sensitivity of the method by 100 to 1000 times that observed with normal Raman. This will improve our sensitivity to the subnanomolar level. Our method of tagging does not affect the unique structural characteristics of the neurotransmitters. It will maintain their structure and provide unique SERRS (SERS + resonance Raman) spectra for each species. The application of this method will be to detect dialysate from in-vivo dialyzed neurotransmitters and to detect the neuro- transmitters in cerebral spinal fluid. This will lead to great improvements over the current methods of HPLC and electrochemical detection. PROPOSED COMMERCIAL APPLICATION: The methodology described in the proposal represents a new and greatly improved method for detection of neurotransmitters. It will have wide application to clinical and research laboratories in the field of neurophysiology.